Facts about Albino Dobermans
Health Effects in Some Forms
of Albinism (Besides Skin Cancer)
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(modified 6/1/04)
Here's just a few examples
of some of the ways in which albinism can affect health:
Amann, J., Ganjam, V. K., & Prieur, D. (1987). Thyroid function
and histology in feline Chediak-Higashi syndrome (CHS). Federation
Proceedings, 46(3), 649.
Amann, J. F., & Prieur, D. J. (1986). Muscle lesions in beige
(Chediak-Higashi syndrome) and heterozygous C57BL/6J mice. Veterinary
Pathology, 23(6), 692-697.
Bachli EB, Brack T, Eppler E, Stallmach T, Trueb RM, Huizing M, Gahl
WA. (2004). Hermansky-Pudlak syndrome type 4 in a patient from Sri
Lanka with pulmonary fibrosis. Am J Med Genet. Jun 1;127A(2):201-7.
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder
characterized by oculocutaneous albinism and a platelet storage pool
deficiency. Some patients also develop fatal pulmonary fibrosis and
some have granulomatous colitis....
Bell, T. G., Meyers, K. M., Prieur, D. J., Fauci, A. S., Wolff, S. M.,
& Padgett, G. A. (1976). Decreased nucleotide and serotonin storage
associated with defective function in Chediak-Higashi syndrome cattle
and human platelets. Federation Proceedings, 35(3), 807.
Bell, T. G., Meyers, K. M., Prieur, D. J., Fauci, A. S., Wolff,
S. M., & Padgett, G. A. (1976). Decreased nucleotide and serotonin
storage associated with defective function in Chediak-Higashi syndrome
cattle and human platelets. Blood, 48(2), 175-184. ...Platelets from
cattle with CHS failed to aggregate in the presence of acid-soluble
collagen, which aggregated normal platelets. ...Serotonin content in
CHS bovine platelets was only about 1.2% of the content in normal
platelets. ATP and ADP contents in bovine CHS platelets were subnormal.
The ATP/ADP ratio in normal platelets was 5.04, as opposed to 29.38 in
CHS platelets. Similar studies were carried out in platelets from human
beings with CHS.
Bennett DC. (2003). The colours of mice and men - 100 genes and
beyond?. Pigment Cell Res, Oct;16(5):576-7. The number of colour genes
in the mouse (genes affecting pigmentation of the hair, skin and eyes)
has now exceeded 100, reaching at least 127 currently (1). Of these,
about 60 or nearly half have been cloned, and all appear to have human
orthologs. These genes can readily be divided into functional sets,
which give some insight into the biological processes required for
normal pigmentation. The largest set controls development and
differentiation of the pigment cells, including for example
transcription factors and growth factors. Mutations in these tend to
give rise to white spotting or total loss of integumentary pigment,
usually without affecting the eyes. The human equivalent mutations
produce congenital white spotting with or without other birth defects
such as deafness. A second set of genes encode protein components of
the melanosome; mutations in these often affect both skin and eyes to
produce oculocutaneous albinism, or altered coat colours in the mouse.
A third set controls the biogenesis of lysosome-related organelles
including the melanosome. Their mutations produce Hermansky-Pudlak
syndrome in humans, and its models (such as cocoa and ruby-eye) in the
mouse. The fourth set is involved in organelle transport, giving
Griscelli syndrome and its models when mutated. Apart from some genes
involved in general metabolic processes like copper transport, a last
set of genes controls eumelanin versus pheomelanin synthesis. Some of
these affect normal hair color in humans. ....
Boissy, R. E., & Nordlund, J. J. (1997). Molecular basis of
congenital hypopigmentary disorders in humans: a review. Pigment Cell
Res, 10(1-2), 12-24. Many specific gene products are sequentially made
and utilized by the melanocyte as it emigrates from its embryonic
origin, migrates into specific target sites, synthesizes melanin(s)
within a specialized organelle, transfers pigment granules to
neighboring cells, and responds to various exogenous cues. A mutation
in many of the respective encoding genes can disrupt this process of
melanogenesis and can result in hypopigmentary disorders. Following are
examples highlighting this scenario. A subset of neural crest derived
cells emigrate from the dorsal surface of the neural tube, become
committed to the melanoblast lineage, and are targeted along the dorsal
lateral pathway. The specific transcription factors PAX3 and MITF
(microphthalmia transcription factor) appear to play a regulatory role
in early embryonic development of the pigment system and in associated
diseases (the Waardenburg syndromes). During the subsequent development
and commitment of the melanoblast, concomitant expression of the
receptors for fibroblasts growth factor (FGFR2), endothelin-B (EDNRB),
and steel factor (cKIT) also appears essential for the continued
survival of migrating melanoblasts. Lack or dysfunction of these
receptors result in Apert syndrome, Hirschsprung syndrome and
piebaldism, respectively. Once the melanocyte resides in its target
tissue, a plethora of melanocyte specific enzymes and structural
proteins are coordinately expressed to form the melanosome and to
convert tyrosine to melanin within it. Mutations in the genes encoding
these proteins results in a family of congenital hypopigmentary
diseases called oculocutaneous albinism (OCA). The tyrosinase gene
family of proteins (tyrosinase, TRP1, and TRP2) regulate the type of
eumelanin synthesized and mutations affecting them result in OCA1,
OCA3, and slaty (in the murine system), respectively. The P protein,
with 12 transmembrane domains localized to the melanosome, has no
assigned function as of yet but is responsible for OCA2 when
dysfunctional. There are other genetically based syndromes,
phenotypically resembling albinism, in which the synthesis of pigmented
melanosomes, as well as specialized organelles of other cell types, is
compromised. The Hermansky-Pudlak syndrome (HPS) and the
Chediak-Higashi syndrome (CHS) are two such disorders. Eventually, the
functional melanocyte must be maintained in the tissue throughout life.
In some cases it is lost either normally or prematurely. White hair
results in the absence of melanocytes repopulating the germinative hair
follicle during subsequent anagen stages. Vitiligo, in contrast,
results from the destruction and removal of the melanocyte in the
epidermis and mucous membranes.
Burns, G. L., Meyers, K. M., & Prieur, D. J. (1984). Secondary
amyloidosis in a bull with Chediak-Higashi syndrome. Canadian Journal
of Comparative Medicine, 48(1), 113-114.
Chieffo, C., Stalis, I. H., Winkle, T. J. v., Haskins, M. E.,
Patterson, D. F., & Van Winkle, T. J. (1994). Cerebellar Purkinje's
cell degeneration and coat color dilution in a family of Rhodesian
Ridgeback dogs. Journal of Veterinary Internal Medicine, 8(2), 112-116.
Chiyonobu T, Yoshihara T, Fukushima Y, Yamamoto Y, Tsunamoto K,
Nishimura Y, Ishida H, Toda T, Kasubuchi Y. (2002). Sister and brother
with Vici syndrome: agenesis of the corpus callosum, albinism, and
recurrent infections. Am J Med Genet, Apr 15;109(1):61-6. A sister and
brother with Vici syndrome are described. They both had oculocutaneous
albinism, agenesis of the corpus callosum, cataracts, and
cardiomyopathy. They were born to healthy unrelated parents, and had
postnatal growth retardation, profound developmental delay, hypotonia,
and cataracts. The sister had recurrent infections, and died of
progressive heart failure at age 19 months. The brother is alive at age
six months with mild cardiomyopathy, and had a single episode of acute
bronchitis at age three months. Review of the clinical manifestations
of the sibs we described and six children reported in the literature
indicates that Vici syndrome is a distinct clinical entity. Its main
clinical manifestations include growth retardation, profound
developmental delay, hypotonia, albinism, agenesis of the corpus
callosum, cataracts, cardiomyopathy, and recurrent infections. The
occurrence of the syndrome in three pairs of sibs of both sexes born to
unaffected parents supports autosomal recessive inheritance.
Collier, L. L., Bryan, G. M., & Prieur, D. J. (1979). Ocular
manifestations of the Chediak-Higashi syndrome in four species of
animals. Journal of the American Veterinary Medical Association,
175(6), 587-590. Ocular examinations performed on cattle, cats, mink,
and mice affected with the Chediak-Higashi syndrome (CHS) revealed
photophobia, pale irises, and fundic hypopigmentation associated with
red fundic light reflections. Cats with CHS also had cataracts.
Spontaneous nystagmus was observed in four of nine cats with CHS, and
the duration of induced nystagmus was longer in affected and Siamese
cats than in clinically normal cats of other breeds. Tear secretion
appeared to be normal in all species of animals with CHS. The ocular
manifestations of CHS in these animals were similar to those reported
in man.
Coupry I, Taine L, Goizet C, Soriano C, Mortemousque B, Arveiler B,
Lacombe D. (2001). Leucodystrophy and oculocutaneous albinism in a
child with an 11q14 deletion. J Med Genet, Jan;38(1):35-8. We report a
patient with an undetermined leucodystrophy associated with type 1A
oculocutaneous albinism (OCA). Type 1 OCA results from recessive
mutations in the tyrosinase gene (TYR) located in 11q14.3. ....
Courtens, W., Broeckx, W., Ledoux, M., & Vamosa, E. (1989).
Oculocerebral hypopigmentation syndrome (Cross syndrome) in a Gipsy
child. Acta Paediatr Scand, 78(5), 806-10. A boy aged 2 years, born
prematurely to Gipsy parents, presented with hypopigmentation severe
encephalopathy with athetoid movements, bilateral ocular anomalies
including cloudy corneas, iris atrophy and cataracts, as well as dental
defects.....the diagnosis of the oculocerebral hypopigmentation
syndrome (Cross syndrome).
Creel, D. (1980). Inappropriate use of albino animals as models
in research. Pharmacol Biochem Behav, 12(6), 969-7. Sensory-neural,
biochemical-metabolic, and physiological anomalies occur in albino
mammals. There are ontogenic and biochemical parallels between the
senses, peripheral nervous system, endocrine glands, metabolism, and
melanin pigmentation. All albino mammals examined have abnormal optic
systems. Many drugs cannot be adequately evaluated in an albino model
because of melanin's ability to bind and interact with some chemicals.
There is evidence that a general reduction in melanin pigment is
correlated with a paucity of amino acids necessary for normal chemical
function of the brain. There is a high probability that enzyme levels
indicative of metabolic performance are deficient in the liver and
kidneys oif albinos. Congenital defects are associated with
hypopigmentation in animal models and human syndromes. Melanin is found
in abundance in the eye, inner ear, and midbrain where neural impulses
are initiated indicating a possible role as an electrophysiologic
mechanism. Microwave irradiation differentially affects albino and
pigmented animals. Implications of these observations and other reports
of anomalies associated with hypopigmentation suggest caution in the
use of albino and other hypomelanotic animals as normal models in
biological research.
Creel, D., Collier, L. L., Leventhal, A. G., Conlee, J. W., &
Prieur, D. J. (1982). Abnormal retinal projections in cats with
Chediak-Higashi syndrome. Investigative Ophthalmology and Visual
Science, 23(6), 798-801. In two Siamese cats with the syndrome,
fragmentation of the A1 layer of the dorsal lateral geniculate nucleus
into several islands was observed by autoradiographic techniques.
del Campo M, Hall BD, Aeby A, Nassogne MC, Verloes A, Roche C, Gonzalez
C, Sanchez H, Garcia-Alix A, Cabanas F, Escudero RM, Hernandez R, Quero
J. (1999). Albinism and agenesis of the corpus callosum with profound
developmental delay: Vici syndrome, evidence for autosomal recessive
inheritance. Am J Med Genet, Aug 27;85(5):479-85. We report on two sibs
and two other unrelated patients with agenesis of corpus callosum,
oculocutaneous albinism, repeated infections, and cardiomyopathy. All
manifested postnatal growth retardation, microcephaly, and profound
developmental delay. Additional central nervous system anomalies
present in at least one patient included hypoplasia of the cerebellar
vermis, white matter neuronal heterotopia, or bilateral schizencephaly.
Repeated viral, bacterial, and fungal infections were consistent with a
primary immunodeficiency. However, immunological studies showed
variable, nonspecific findings. Cardiomyopathy with progressive heart
failure or infection led to death before age 2 years in three of the
patients. ....
Dube P, Der Kaloustian VM, Demczuk S, Saabti H, Koenekoop RK. (2000). A
new association of congenital hydrocephalus, albinism, megalocornea,
and retinal coloboma in a syndromic child: a clinical and genetic
study. Ophthalmic Genet. Dec;21(4):211-6. We describe a child with
global developmental delay, prominent metopic suture, trigonocephaly,
and cryptorchidism whose symptoms resemble the well-known 9p deletion
syndrome or 9p monosomy. We also noted congenital hydrocephalus,
oculocutaneous albinism, retinal coloboma, and megalocornea, which are
not typical features of 9p monosomy. ....
Duran McKinster, C., Rodriguez Jurado, R., Ridaura, C., de la Luz
Orozco Covarrubias, M., Tamayo, L., & Ruiz Maldonando, R. (1999).
Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical
and morphological findings in 7 patients. Arch Dermatol, 135(2), 182-6.
BACKGROUND: Silvery hair and severe dysfunction of the central nervous
system (neuroectodermal melanolysosomal disease or Elejalde syndrome)
characterize this rare autosomal recessive disease. Main clinical
features include silver-leaden hair, bronze skin after sun exposure,
and neurologic involvement (seizures, severe hypotonia, and mental
retardation). Large granules of melanin unevenly distributed in the
hair shaft are observed. Abnormal melanocytes and melanosomes and
abnormal inclusion bodies in fibroblasts may be present. Differential
diagnosis with Chediak-Higashi syndrome and Griscelli syndrome must be
done. ....
Feng, G. H., Bailin, T., Oh, J., & Spritz, R. A. (1997).
Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome
and contains a rare 'AT-AC' intron. Hum Mol Genet, 6(5), 793-7.
Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal
recessive disorder in which albinism, bleeding and lysosomal storage
are associated with defects of diverse cytoplasmic organelles,
including melanosomes, platelet dense granules and lysosomes. Similar
multi-organellar defects occur in the Chediak-Higashi syndrome (CHS),
as well as in a large number of different mouse mutants.....
Griffiths GM. (2002). Albinism and immunity: what's the link? Curr Mol
Med, Aug;2(5):479-83. A small number of inherited diseases show a
combination of immunological and pigmentation defects. Chediak-Higashi,
Griscellis and Hermansky-Pudlak syndromes are all autosomal recessive
diseases with these characteristics. Recent advances in both the
identification of the genes giving rise to these diseases and the cell
biology of immune cells and melanocytes have begun to reveal the
molecular links between immunodeficiencies and albinism. These studies
identify key proteins, such as Rab27a, which are critical for secretion
of specialised granules found in melanocytes and immune cells. The
granules of these cells are modified lysosomes termed 'secretory
lysosomes'. These studies reveal that secretory lysosomes use
specialised mechanisms of secretion, not found in other cell types,
which explains the selective defects in these diseases.
Griscelli, C., Durandy, A., Guy Grand, D., Daguillard, F., Herzog, C.,
& Prunieras, M. (1978). A syndrome associating partial albinism and
immunodeficiency. Am J Med, 65(4), 691-702. Two unrelated patients with
partial albinism, frequent pyogenic infections and acute episodes of
fever, neutropenia and thrombocytopenia are described. Their pigmentary
dilution was characterized by large clumps of pigments in the hair
shafts and an accumulation of melanosomes in melanocytes. Melanocytes
had few short dendritic expansions, and keratinocytes were
hypopigmented. No or few Langerhans' cells were detected in skin by
electron microscopy and ATP-ase reactions. This pigmentary dilution,
different from all other human albinisms, resembles the unique defect
of the mutant dilute (d-d) mouse. Despite the presence of an adequate
number of T and B lymphocytes, the patients were hypogammaglobulinemic,
deficient in antibody production and incapable of manifesting delayed
skin hypersensitivity or of rejecting skin grafts. Their leukocytes did
not stimulate normal lymphocytes and could not generate cytotoxic cells
during mixed leukocyte reaction. T lymphocytes of one patient were
unable to exert a helper effect on the maturation of B lymphocytes into
immunoglobulin-containing cells following in vitro stimulation with
pokeweed mitogen.....
Gul D, Odabas E, Kutlu M. (2000). Oculocutaneous albinism and reduced
bone density in two sibs: a new autosomal recessive syndrome? Clin
Dysmorphol, Oct;9(4):295-6. A sister and brother, with oculocutaneous
albinism and reduced bone density are described. Autosomal recessive
inheritance is possible. This association has not been previously
described.
Klein, C., Philippe, N., Le Deist, F., Fraitag, S., Prost, C., Durandy,
A., Fischer, A., & Griscelli, C. (1994). Partial albinism with
immunodeficiency (Griscelli syndrome). J Pediatr, 125(6 Pt 1), 886-95.
Partial albinism with immunodeficiency is a rare and fatal immunologic
disorder characterized by pigmentary dilution and variable cellular
immunodeficiency. ....Primary abnormalities included a silvery-grayish
sheen to the hair, large pigment agglomerations in hair shafts, and an
abundance of mature melanosomes in melanocytes, with reduced
pigmentation of adjacent keratinocytes. Clinical onset occurred between
the ages of 4 months and 4 years and was characterized by accelerated
phases (lymphohistiocytic infiltration of multiple organs, including
the brain and the meninges), triggered by viral and bacterial
infections. Characteristic laboratory features included pancytopenia,
hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia.
Consistent immunologic abnormalities were characterized by absent
delayed-type cutaneous hypersensitivity and impaired natural killer
cell function. Some patients had secondary hypogammaglobulinemia,
impaired major histocompatibility complex-mediated cytotoxic effects, a
decreased capacity of lymphocytes to trigger a mixed lymphocyte
reaction, or various functional granulocytic abnormalities. The disease
seems to be invariably lethal without bone marrow transplantation; the
mean age at the time of death was 5 years. ....
Kramer, J. W., Davis, W. C., & Prieur, D. J. (1975). An inherited
condition of enlarged leukocytic and melanin granules in cats: probable
homology with the Chediak-Higashi syndrome. Federation Proceedings,
34(No.3), 861. The Chediak-Hagashi syndrome (CHS) is an autosomal
recessive condition manifested morphologically by enlarged cytoplasmic
granules in many cell types. CHS has been described in man, mink,
cattle, mice and in a killer whale. A condition in a line of Persian
cats which resembles CHS was recently observed. Enlarged cytoplasmic
granules were present in leucocytes and melanophores in all the Persian
cats (4) with yellow eyes and the 'Blue Smoke' coat colour which were
examined, but were absent in related cats without the specified ocular
and coat colours. Analysis of the pedigree of this family of cats
suggests that the trait is inherited as an autosomal recessive
condition. Round acidophilic cytoplasmic inclusions varying in diameter
from 1 to 2 mu were present in Wright's stained neutrophils. These
inclusions were detected in neutrophils from the myeloblast to the
segmented stage. Electron microscopic cytochemistry revealed enlarged
peroxidase-positive granules which thus correspond to azurophilic
(primary) granules. Hair and skin from these cats contained enlarged
melanin granules as compared to normal cats. Although an increased
susceptibility to infection was not apparent, a bleeding tendency was
present in these cats. The evidence suggests that the condition in
these cats is homologous with CHS.
Kramer, J. W., Davis, W. C., & Prieur, D. J. (1977). The
Chediak-Higashi syndrome of cats. Laboratory Investigation, 36(5),
554-562. Initial clinical, genetic, cytochemical, and ultrastructural
studies were carried out to characterize the Chediak-Higashi syndrome
in cats. Three cats with Chediak-Higashi syndrome were found in a
single line of 27 Persian cats, and three additional affected cats were
produced from two prospective breedings of the original line. The
disorder was characterized genetically as an autosomal recessive
condition. All cats in the line with the combination of yellow eye
color and "blue smoke" hair colour exhibited the disorder. Four of the
five cats examined had bilateral nuclear cataracts as early as three
months of age. No increased susceptibility to infectious disease was
observed. A bleeding tendency was noted. Abnormally large eosinophilic,
sudanophilic, peroxidase-containing granules were observed in the
neutrophiles of the granulocytic series of blood and bone marrow by
electron and light microscopy. Granules of eosinophiles and basophiles
were also enlarged. Light microscopic studies of hair and skin revealed
enlarged melanin granules. These manifestations were similar to those
in man, mink, cattle, mice, and the killer whale with Chediak-Higashi
syndrome. Cats are the sixth species in which this genetic disease has
been reported.
Lyerla TA, Rusiniak ME, Borchers M, Jahreis G, Tan J, Ohtake P, Novak
EK, Swank RT. (2003). Aberrant lung structure, composition, and
function in a murine model of Hermansky-Pudlak syndrome. Am J Physiol
Lung Cell Mol Physiol. Sep;285(3):L643-53. Hermansky-Pudlak syndrome
(HPS) is a genetically heterogeneous inherited disease causing
hypopigmentation and prolonged bleeding times. An additional serious
clinical problem of HPS is the development of lung pathology, which may
lead to severe lung disease and premature death. ....
Mancini, A. J., Chan, L. S., & Paller, A. S. (1998). Partial
albinism with immunodeficiency: Griscelli syndrome: report of a case
and review of the literature. J Am Acad Dermatol, 38(2 Pt 2), 295-300.
Partial albinism with immunodeficiency (Griscelli syndrome) is an
uncommon disorder characterized by pigmentary dilution and variable
immunodeficiency. Features include a silvery-gray sheen to the hair,
large clumped melanosomes in hair shafts, and prominent mature
melanosomes in cutaneous melanocytes with sparse pigmentation of
adjacent keratinocytes. Immunologic abnormalities most often include
impaired natural killer cell activity, absent delayed-type
hypersensitivity, and impaired responses to mitogens.....The
syndrome...carries a poor prognosis without bone marrow
transplantation. We describe a patient with Griscelli syndrome who
presented with hepatosplenomegaly, hepatitis, pancytopenia, and silvery
hair in the newborn period.
Martinez-Arias R, Comas D, Andres A, Abello MT, Domingo-Roura X,
Bertranpetit J. (2000). The tyrosinase gene in gorillas and the
albinism of 'Snowflake'. Pigment Cell Res, Dec;13(6):467-70. The
sequence of the tyrosinase (Tyr) gene coding tracts has been obtained
for the gorilla (Gorilla gorilla gorilla). The five exons of the gene
were sequenced in three gorillas and in a normally pigmented human. The
tyrosinase gene has been found to be a very conserved locus with a very
low substitution rate. Some nucleotide and amino acid differences were
found between the gorilla and human tyrosinase coding sequences. One of
the gorillas included in the study is the only known case of albinism
in a gorilla ('Snowflake'). Mutations of the TYR gene lead to
Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism
in humans (OMIM accession number 203100). The TYR gene encodes the
tyrosinase enzyme (E.C. 1.14.18.1), whose activity was found to be
completely lacking in 'Snowflake', indicating that a mutation in the
Tyr gene is the likely cause of his albinism. Nonetheless, no
nucleotide changes were detected that could account for the lack of Tyr
product or tyrosinase activity in Snowflake, and explanations of these
findings are discussed. (an added note: Snowflake recently died of
squamous cell carcinoma)
McGarry, M. P., Reddington, M., Novak, E. K., & Swank, R. T.
(1999). Survival and lung pathology of mouse models of Hermansky-Pudlak
syndrome and Chediak-Higashi syndrome. Proc Soc Exp Biol Med, 220(3),
162-8. Hermansky-Pudlak Syndrome (HPS), a recessively inherited disease
in humans, affects the biosynthesis/processing of the related
intracellular organelles: lysosomes, melanosomes, and platelet dense
granules. ....Mice doubly homozygous for the pale ear and ruby eye or
for the muted and pearl genes had the shortest life spans with none
surviving the two-year experimental duration. Life spans were similarly
severely reduced in the beige and gunmetal mutants. Intermediate life
spans were apparent in the pearl, pallid, and cocoa mutants whereas
minimal effects were noted in ruby eye, muted, light ear, and cocoa
mutants. ....
Meyers, K. M., Seachord, C. I., Prieur, D., & Holmsen, H. (1979). A
serotonin induced biphasic aggregation by platelets from cats with the
Chediak-Higashi syndrome. Thrombosis and Haemostasis, 42(1), 195.
Mottonen M, Lanning M, Baumann P, Saarinen-Pihkala UM. (2003).
Chediak-Higashi syndrome: four cases from Northern Finland. Acta
Paediatr, Sep;92(9):1047-51. Chediak-Higashi syndrome (CHS) is a rare
multiorgan disease entity with autosomal recessive inheritance
characterized by oculocutaneous albinism, bleeding tendency, recurrent
bacterial infections and various neurological symptoms. Intracellular
vesicle formation is deficient, resulting in giant granules in many
cells, e.g. giant melanosomes in the melanocytes. Diagnosis has been
based on morphological examination of peripheral blood and bone marrow,
with giant granules seen in cells of the myeloid lineage and in
lymphocytes. The ultimate diagnostic test is to look for a mutated LYST
gene. Most patients develop an accelerated phase of the disease with
deposition of lymphohistiocytes in the liver, spleen, lymph nodes and
bone marrow, resulting in hepatosplenomegaly, bone marrow infiltration
and haemophagocytosis. Peripheral blood neutropenia becomes more
profound as anaemia and thrombocytopenia develop. Most patients succumb
before the age of 10 years. ....
Oh, J., Bailin, T., Fukai, K., Feng, G. H., Ho, L., Mao, J. I.,
Frenk, E., Tamura, N., & Spritz, R. A. (1996). Positional cloning
of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic
organelles [see comments]. Nat Genet, 14(3), 300-6. Hermansky-Pudlak
syndrome (HPS) is an often-fatal autosomal recessive disease in which
albinism, bleeding, and lysosomal storage result from defects of
diverse cytoplasmic organelles: melanosomes, platelet dense bodies, and
lysosomes. ....
Pastural, E., Barrat, F. J., Dufourcq Lagelouse, R., Certain, S.,
Sanal, O., Jabado, N., Seger, R., Griscelli, C., Fischer, A., & de
Saint Basile, G. (1997). Griscelli disease maps to chromosome 15q21 and
is associated with mutations in the myosin-Va gene. Nat Genet, 16(3),
289-92. Griscelli disease (OMIM 214450) is a rare autosomal recessive
disorder characterized by pigmentary dilution, variable cellular
immunodeficiency and onset of acute phases of uncontrolled lymphocyte
and macrophage activation, leading to death in the absence of
bone-marrow transplantation.....
Penner, J. D., & Prieur, D. J. (1986). Homology of Chediak-Higashi
syndrome in humans, cats, and mink. [Abstract]. Proceedings of the
Society for Experimental Biology and Medicine, 181(1), 196.
Prieur, D. J. (1972). Defective function of renal lysosomes in mice
with the Chediak-Higashi syndrome. Dissertation Abstracts
International, 32b(No.8), 4933.
Prieur, D. J., & Collier, L. L. (1978). Animal model of human
disease: Chediak-Higashi syndrome. Animal model: Chediak-Higashi
syndrome of animals. American Journal of Pathology, 90(2), 533-536.
Prieur, D. J., & Collier, L. L. (1987). Neutropenia in cats with
the Chediak-Higashi syndrome. Canadian Journal of Veterinary Research,
51(3), 407-408. Neutropenia is often present in human patients with
Chediak-Higashi syndrome, but has not been reported in affected
animals. This study confirms that affected cats have neutropenia,
whereas unaffected cats genotypically heterozygous for the syndrome do
not. No lysozyme activity was detected in the serum.
Sanal, O., Kucukali, T., Ersoy, F., Tinaztepe, K., & Gogus, S.
(1993). Griscelli's syndrome: clinical features of three siblings. Turk
J Pediatr, 35(2), 115-9 Issn: 0041-4301. Three siblings diagnosed as
having Griscelli's syndrome (GS) are presented. The clinical features
were partial albinism, silvery hair and absence of giant granules in
the white blood cells. ....The first sibling died at the age of two,
having a clinical picture suggestive of bulbar poliomyelitis. However,
no tissue was available for histopathologic examination. The second
sibling developed fever, jaundice, seizure, hepatosplenomegaly and
lymphadenopathy and died at the age of six. Postmortem examination of
this sibling revealed lymphohistiocytosis in the liver and spleen. The
propositus died at the age of five following development of central
nervous system involvement. Immunologic studies were not available in
the first sibling. The IgG level was slightly low and the T-lymphocyte
number was normal in the second sibling. The propositus had normal
serum immunoglobulin levels and T-cell numbers and skin tests were
positive with phytohemagglutinin and candida.
Scheinfeld NS. (2003). Syndromic albinism: a review of genetics and
phenotypes. Dermatol Online J, Dec;9(5):5. There are several syndromes
of albinism associated with systemic pathology. These include
Chediak-Higashi Syndrome (CHS), Hermansky-Pudlack Syndrome (HPS),
Griscelli Syndrome (GS), Elejalde Syndrome (ES) and
Cross-McKusick-Breen Syndrome (CMBS). In the last several years the
genetic defects underlying some of these syndromes have been described.
HPS is related to 7 genes in humans. GS is related to 3 genes: MYOVA,
Rab-27A, and melanophilin (Mlph). CHS is related to one gene: LYST. The
genetic defects in ES and CMBS are yet to be defined. Syndromic forms
of albinism are associated with defects in the packaging of melanin and
other cellular proteins. As such they are distinct from oculocutaneous
albinism, which is associated with defects in the production of melanin
(e.g., TRP1, P gene, and tyrosinase).
Searle, A. G. (1990). Comparative genetics of albinism. Ophthalmic
Paediatr Genet, 11(3), 159-64. ....The optic track misrouting found in
human albinos also occurs in albino alleles in other mammals, which may
also show reduced activity and stress responses.....in the mouse,
[albinistic mutations] are associated with defects of kidney, liver and
thymus. Tyrosinase-positive albinos or near-albinos are known at a
number of loci in mice and other mammals. They are the result of the
absence or inhibition of melanocytes in the affected areas, so that no
melanin is produced. In general they are associated with pathological
pleiotropisms which may lead to anaemia, inner ear defects, megacolon,
neurological effects, skeletal defects, microphthalmia, osteopetrosis,
spina bifida, sterility and so on.....
Silveira-Moriyama L, Moriyama TS, Gabbi TV, Ranvaud R, Barbosa ER.
(2004). Chediak-Higashi syndrome with parkinsonism. Mov Disord,
Apr;19(4):472-5. Chediak-Higashi syndrome (CHS), typically presents
with partial albinism and severe hematological abnormalities. About 10%
of the patients have a mild adult form associated with various
neurological manifestations....
Verheij JB, Kunze J, Osinga J, van Essen AJ, Hofstra RM. (2002). ABCD
syndrome is caused by a homozygous mutation in the EDNRB gene. Am J Med
Genet, 2002 Mar 15;108(3):223-5. ABCD syndrome is an autosomal
recessive syndrome characterized by albinism, black lock, cell
migration disorder of the neurocytes of the gut (Hirschsprung disease
[HSCR]), and deafness. ....
Ziakas NG, Jogiya A, Michaelides M. (2004). Eye. A case of familial
trichomegaly in association with oculocutaneous albinism type 1..
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