Dermatologica Sinica

: 2019  |  Volume : 37  |  Issue : 4  |  Page : 235--236

Hypohidrosis as a clue to the early diagnosis of fabry disease and prevention of late complications

Tzu-Chien Hsu1, Chao-Chun Yang1, Chou-Ching Ling2, Chaw-Ning Lee3,  
1 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 Department of Neurology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3 Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan

Correspondence Address:
Dr. Chaw-Ning Lee
Department of Dermatology, College of Medicine and Hospital, National Cheng Kung University, 138 Sheng-Li Rd., Tainan

How to cite this article:
Hsu TC, Yang CC, Ling CC, Lee CN. Hypohidrosis as a clue to the early diagnosis of fabry disease and prevention of late complications.Dermatol Sin 2019;37:235-236

How to cite this URL:
Hsu TC, Yang CC, Ling CC, Lee CN. Hypohidrosis as a clue to the early diagnosis of fabry disease and prevention of late complications. Dermatol Sin [serial online] 2019 [cited 2020 Oct 24 ];37:235-236
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Full Text

Dear Editor,

A 23-year-old male without underlying diseases presented with hypohidrosis for 8 years. He reported that he fainted easily in hot environments and during exercise. He denied any history of epistaxis. The patient also mentioned tingling pain sensation over his palms and soles since childhood. Besides, he had intermittent diarrhea after dairy intake and orthostatic dizziness. The skin biopsy 3 years ago on upper back showed normal-appearing skin with preserved sweat glands. However, hypohidrosis persisted [Figure 1]e. Physical examination did not reveal any abnormalities of hair and nail, but telangiectasia over his lips, hard palate, palms, and soles was noted [Figure 1]a and b]. There was also the presence of angiokeratomas over his penis and scrotum [Figure 1]c. With regard to family history, the aunt on his mother's side had similar lesions on the palms and soles with complaints of frequent epistaxis. The parents and sister of the patient did not have relevant symptoms and signs.{Figure 1}

Ophthalmological examinations showed corneal verticillata and vessel tortuosity over the fundus and conjunctiva. Tilting table study did not show evidence of orthostatic hypotension. Nerve conduction velocity test revealed left posterior tarsal tunnel syndrome and bilateral cubital tunnel syndrome. Enzyme activity test of the blood showed deficiency of α-galactosidase at the level of 0.24 (normal range: 60.6 ± 27.19) nmol/mg protein (prot)/h and β-galactosidase at the level of 79.4 (normal range: 93.85 ± 25.75) nmol/mg prot/30 min. Genetic testing revealed hemizygous mutation (c.658C>T, p.R220X in the 5th exon) in alpha-galactosidase (GLA) gene [Figure 1]d on the X chromosome, which confirmed the diagnosis of Fabry disease. His mother was a heterozygous carrier of the same mutation [Figure 2] and had elevated plasma globotriaosylsphingosine (Lyso-Gb3: 2.310 ng/mL, normal: <0.8), a metabolite which is regarded as the standard test to identify the female carrier of Fabry disease. The genetic and metabolite workup in his sister was normal [Figure 2]. His father had normal blood level of α-galactosidase and β-galactosidase and therefore did not receive the genetic analysis.{Figure 2}

Before the diagnosis of Fabry disease was confirmed, the patient had an episode of acute numbness over the left face and left upper limbs. Magnetic resonance imaging (MRI) showed ischemic stroke in the right temporal subcortical region.

The patient received agalsidase alfa infusion (0.2 mg/kg) for 1 year then switch to agalsidase beta infusion (1 mg/kg) due to the adverse effect of tachycardia and chillness. At 4th months of agalsidase beta treatment, he suffered from another episode of stroke and MRI showed a new insult at the left posterior medulla oblongata. There was no cardiovascular event or renal impairment.

In 1898, Johannes Fabry and William Anderson described the first case of Fabry disease.[1] It is characterized as an X-linked recessive inherited lysosomal storage disorder resulting from the deficient or absent activity of the lysosomal enzyme, α-galactosidase A. The enzymatic defect leads to the systemic accumulation of globotriaosylceramide (GL-3) and related glycosphingolipids in the plasma and in tissue lysosomes.[2] Males are primarily affected, with the initial symptoms manifesting during childhood, which typically present as acroparesthesias and episodic attacks of excruciating pain, known as Fabry crises, which are triggered by fevers, exercise, stress, and/or dramatic changes in the weather. Other clinical features include hypohidrosis or even anhydrosis, along with angiokeratomas which typically present on the abdomen, buttocks, flanks, penis, and scrotum. Patients in early adulthood also have corneal opacities, postprandial abdominal cramping, diarrhea, left ventricular hypertrophy, and proteinuria. With advancing age, the progressive lysosomal GL-3 accumulation, particularly in the vascular endothelium, leads to renal failure and vascular disease of the heart and the brain.[2],[3] Heterozygous females might develop mild-to-severe symptoms. In the absence of family history, the disease is often ignored or only recognized when patients present with severe complications in its late stages. Since the incidence of Fabry disease in Taiwan was not low (1:1250 in male newborns),[4] and this disease is not included in the official routine screening list for newborns, it is very important to diagnose the disease in the early stage before the serious complications occur.

Due to the earliest manifestations of typical skin features, dermatologists are often the first to make the diagnosis.[5] Early treatment such as enzyme replacement therapy for Fabry disease can prevent severe and late complications, which has been shown to clear the accumulated GL-3 in the blood vessels as well as in the cells of the heart, kidney, and skin.[6] Agalsidase alfa and beta were considered similar pharmaceutical agents; however, in our patient with tachycardia and chillness, who was suspected in association with agalsidase alfa infusion, he then received agalsidase beta treatment.

The severe complication of Fabry disease, including stroke, usually occurs in young age,[7] and therefore, an early diagnosis and treatment to prevent these debilitating sequels is very important. We report this case to highlight the presentation of hypohidrosis in Fabry disease and to increase the awareness of physicians to include Fabry disease in the differential diagnosis when encountering patients with hypohidrosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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1Anderson W. A case of angiokeratoma. Br J Dermatol 1898;10:113.
2Desnick RJ, Ioannou YA, Eng CM. α-Galactosidase A deficiency: Fabry disease In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Volgelstein B, (eds): The Metabolic and Molecular Bases of Inherited Disease. 8th ed, McGrawHill, New York, 2001. p. 3733-74.
3Kotnik J, Kotnik F, Desnick RJ. Fabry disease. A case report. Acta Dermatovenerol Alp Pannonica Adriat 2005;14:15-9.
4Hwu WL, Chien YH, Lee NC, Chiang SC, Dobrovolny R, Huang AC, et al. Newborn screening for fabry disease in Taiwan reveals a high incidence of the later-onset GLA mutation c.936+919G&gt; A (IVS4+919G&gt; A). Hum Mutat 2009;30:1397-405.
5Jung SE, Kim YC. Hypohidrosis: An early clue in the diagnosis of fabry disease. Clin Exp Dermatol 2015;40:444-5.
6Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med 2001;345:9-16.
7Share JB. Review of drug treatment for Down's syndrome persons. Am J Ment Defic 1976;80:388-93.