JOURNAL OF THE ROYAL SOCIETY OF MEDICINE

Oculocutaneous albinism
and bruising in two sistersprobable Hermansky-Pudlak
syndrome

Volume 88

May 1995

20S

601

Julia P Ellis FRCP DCH Atherton Gray MD MRCPath

Frances Richards FRCS FRCOphth

80X

1001

J R Soc Med 1995;88:293P-294P

CASE PRESENTED TO SECTION OF DERMATOLOGY, 18 NOVEMBER 1993

Keywords: oculocutaneous albinism; Hermansky-Pudlak syndrome

Cases of Hermansky-Pudlak syndrome may present to

the dermatologist, ophthalmologist or haematologist.
Classically the diagnosis rests on the triad of
oculocutaneous albinism, a bruising tendency and the
presence of characteristic pigmented-containing cells in
the bone marrowl. Specific tests of platelet function
can, however, suggest the diagnosis without recourse to
invasive techniques. We describe the disease in two
young sisters.

CASE REPORT
Both sisters (EG born 3.10.88 and CG born 3.9.91) were
noted to have 'funny' eyes at birth and were later found to
have nystagmus and fair skin. A diagnosis of tyrosinasepositive oculocutaneous albinism was made. Both started
bruising easily when they began to walk and EG had several
minor nose bleeds. The parents were non-consanguinous
with normal skin pigmentation, visual function and no

history of bruising.
The physical findings in both children were the same,
namely horizontal nystagmus, blue irides and albinoid fundi.
The fundi were pale with prominent choroidal vessels due to
the lack of pigment in the choroid and retinal pigment
epithelium. EG was significantly myopic and CG had mild
hypermetropia. Their skin was fair and they had fair but not
white hair. EG became sunburnt after minimal sun exposure.
EG had a normal full blood count, blood film and
clotting screen. The template bleeding time slightly
prolonged (10.5 min). Platelet function tests (Figure 2)
showed primary aggregation with adenosine diphosphate
(ADP) with no secondary aggregation when compared to
normal controls (Figure 1). Platelet ADP and adenosine
triphosphate (ATP) were assayed in both children and
Pnncess Margaret HospiW, Okus Road, Swindon, SN1 4JU, Wilts. UK
Correspondence to: Dr Julia Ellis

Time (min)
Figure 1 Platelet aggregation. Patient EG

201
'01

601
801

1001
4
3
Time (min)
Figure 2 Platelet aggregation. Normal control

parents (Table 1). The platelet ADP content was reduced in

EG and CG had an increased ATP/ADP ratio.
Advice was given on the avoidance of sun exposure and
the use of high protection sun screens to reduce the risk of
sunburn and cutaneous neoplasia. Appropriate corrective
and tinted lenses were prescribed. Aspirin, non-steroidal
anti-inflammatories and intramuscular injections were
contraindicated and limitations were advised on activities
which carried a risk of trauma. Platelet transfusions were
reserved for the treatment of major bleeding and as
prophylaxis for surgery. Infusions of DDAVP (desmopressin)
and cryoprecipitate2 have also been reported to reduce the

bleeding tendency.
DISCUSSION

Two siblings with tyrosinase-positive oculocutaneous

albinism were investigated for a bruising tendency.
Abnormal platelet function in the older child was
demonstrated by a slightly prolonged bleeding time and
failure of secondary platelet aggregation. A storage pool
defect of platelets was demonstrated in both children by the
reduced ADP content of the platelets (Table 1) and a
diagnosis of Hermansky-Pudlak syndrome (HPS) was made.

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JOURNAL OF THE ROYAL SOCIETY OF MEDICINE

Table 1 Platelet nuclootides Platelet concentrations of adenosine

triphosphate (ATP) and adenosine diphosphate (ADP).
Normal range

(nmIlO8

Total
ATP
ADP
ATP/ADP ratio

EG

CG

Mother Father

platelets)

6.6
4.3
2.3
1.9

5.9
4.1
1.8
2.3

7.4
4.8
2.7
1.8

5-12
3.5-8
2.5-6
1.0-2.2

7.2
4.9
2.4
2.1

Volume 88

May 1995

There is some evidence that the platelet defect may be a

quantitative or qualitative abnormality of a dense body
membrane protein leading to impaired storage of
nucleotides6. It may be that an analogous protein deficiency
in the melanosome membrane could account for the tyrosinasepositive albino phenotype where melanogenesis itself is normal.
Awareness of the diagnosis is important in the prevention
of skin disease, in the optimization of visual function and in
the haematological management of surgery and trauma.
REFERENCES

The platelet defect in HPS is associated with reduced

storage of adenine nucleotides3 which are important in the
platelet release reaction. An identical platelet defect has been
described which is not associated with albinism4 but the
pattern of inheritance appears to be autosomal dominant in
those cases not recessive as in HPS and the present cases.
Only a minority of albino patients have a platelet defect or
suffer from a bleeding tendency5 and not all have abnormal
pigment-containing cells in the marrow. Nevertheless the
combination of albinism, probable recessive inheritance and
storage pool defect of platelets in these children made the
diagnosis of HPS sufficiently likely that the need for bone
marrow biopsy was avoided.
The cause of HPS is likely to be a single gene mutation5 but
a common molecular abnormality has not been identified.

Cold urticaria, raised IgE

and HIV infection
R C Yu MD MRCP1

B Evans FRCP2

J J Cream FRCP1

J R Soc Med 1 995;88:294P-295P

CASE PRESENTED TO SECTION OF DERMATOLOGY, 16 MAY 1994

Keywords: cold urticaria; IgE; human immunodeficiency virus; acquired

immunodjiciency syndrome
We present a patient with cold urticaria as an unusual
and late cutaneous manifestation of acquired
immunodeficiency syndrome. The severe CD4 cell
depletion and markedly elevated serum IgE levels in our
patient provide some insights into certain aspects of
immune regulatory mechanisms.
Departments of 1 Dermatology and 2GenHtourinary Medicine, Charing Cross and
Westminster Medical School, Du Cane Road, London W12 ONN, UK

294P

Correspondence to: Dr Raymond Yu, Unit of Dermatology, Royal Postgraduate

Medical School

1 Hermansky F, Pudlak P. Albinism associated with hemmorrhagic

diathesis and unusual pigmented reticular cells in the bone marrow:
report of two cases with histochemical studies. Blood 1959;14:162-9
2 Wijermans PW. Hermansky Pudlak syndrome: correction of bleeding
time by l-desamino-8D-arginine vasopressin. Am jHematol 198;30: 154-7
3 White JG, Edson JR, Desnick SJ, Witkop CJ. Studies of platelets in a
variant of the Hermansky-Pudlack syndrome. AmJ Pathol 1971;63:319
4 Weiss HJ, Chevernick PA, Zalusky R, Factor A. A familial defect in
platelet function associated with impaired release of adenine diphosphate.
N Englj Med 1969;281:1264
5 Hardisty RM, Mills DCB, Ketsa-ard K. The platelet defect associated
with albinism. BrJ Haem 1972;23:679-92
6 Gerrard JM, Lint D, Sims PJ, et a). Identification of a platelet dense
granule membrane protein that is deficient in a patient with the
Hermansky Pudlak syndrome. Blood 1991;77:101-12

(Accepted I August 1994)

CASE REPORT

A 38-year old woman contracted human immunodeficiency

virus (HIV) infection through intravenous drug abuse in
Spain between 1977 and 1985. Her circulating CD4 count
had fallen below 10/mm3 by 1992. Despite treatment with
azidothymidine (AZT) and dapsone she developed culturepositive Pneumocystis carinii pneumonia in June 1992. After
recovering from her pneumonia, she continued to feel
unwell for many months with recurrent fever, severe
gastrointestinal symptoms and uro-genital ulcerations. She
received a variety of medications including antibiotics,
antifungals, acyclovir and didanosine (DDI). In August
1993, she developed itchy papules on her face and flank,
and noticed abnormal skin reaction to the cold. Several
drugs were stopped with no improvement. In January
1994, she was referred to the dermatology department
with cold-contact urticaria which could be triggered by a
cool breeze, and cold water immersion. Iced drinks or ice
cream caused swelling in her throat. Clinical examination
revealed erythematous urticated papules along her jawline
and over the loins. Application of an ice cube to her
forearm for 30 s resulted in an immediate marked flare and
wheal reaction.