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Year : 2020  |  Volume : 21  |  Issue : 4  |  Page : 354-355

H syndrome: A rare case with homozygous mutation in SLC29A3 gene

1 Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
2 Department of Pediatric Endocrinology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India
3 Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India

Date of Submission10-Apr-2020
Date of Decision26-Apr-2020
Date of Acceptance04-May-2020
Date of Web Publication30-Sep-2020

Correspondence Address:
Sahana M Srinivas
Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_58_20

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How to cite this article:
Srinivas SM, Thimmaiah SG, Venkatesan R, Palany R. H syndrome: A rare case with homozygous mutation in SLC29A3 gene. Indian J Paediatr Dermatol 2020;21:354-5

How to cite this URL:
Srinivas SM, Thimmaiah SG, Venkatesan R, Palany R. H syndrome: A rare case with homozygous mutation in SLC29A3 gene. Indian J Paediatr Dermatol [serial online] 2020 [cited 2020 Oct 19];21:354-5. Available from: https://www.ijpd.in/text.asp?2020/21/4/354/296863


H syndrome is a rare autosomal recessive genodermatosis caused by mutation in the SLC29A3 gene encoding the nucleoside transporter hENT3.[1] Approximately 130 cases have been described in the literature so far, and most of them from Arab population. There are only a few cases described from the Indian population, especially with completed genetic analysis.[2] The unique features of this syndrome are symmetrical hyperpigmentation of skin along with hypertrichosis, sclerodermoid changes, hearing loss, heart anomalies, hepatosplenomegaly, hypergonadotropic hypogonadism, hyperglycemia (insulin-dependent diabetes mellitus), hypertriglyceridemia, short height, and hallux valgus.[3] There are >20 different pathogenic mutations in SLC29A3 described, and most of them are missense mutations in exon 6.[3] We describe an 11-year-old girl with characteristic features of H syndrome confirmed by genetic analysis.

An 11-year-old Indian, term girl, born to consanguineous parents presented with asymptomatic hyperpigmentation and hardening of the skin over both lower limbs and back from 3 years and failure to thrive along with stunting and wasting for nearly a year. She was prepubertal with type 1 diabetes mellitus and had bilateral sensorineural hearing loss for which she was using a hearing aid. She had recurrent blood transfusions in the past for severe anemia. Developmental milestones and sibling history were normal. There was a history of a paternal aunt having hyperpigmentation with hair growth in the lower limbs. General physical examination showed clubbing, lymphadenopathy (cervical and axillary), short stature (height 115 cm, <3rd percentile), underweight (18 kg, <3rd percentile), low set ears, proptosis, and perilimbal congestion. Cutaneous examination showed well- to ill-defined bilaterally symmetrical hyperpigmented plaques along with induration and hypertrichosis on the lumbosacral area, thighs, lower legs, and dorsum of feet sparing the knee joints, gluteal region and some part of popliteal fossae [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Bilateral flat feet and hallux valgus were seen. Systemic examination was noncontributory except for hepatosplenomegaly. Laboratory investigations showed anemia (hemoglobin [Hb]-10.1 g/dl), fasting blood glucose levels (257 mg/dl), 2-h postprandial blood sugars (208 mg/dl), and glycated Hb of 11.6%. Lipid profile, thyroid profile, antinuclear antibody, chest radiography, and electrocardiogram were normal. Two-dimensional echocardiography showed mild pericardial effusion. Ultrasound abdomen showed fatty changes in the liver with hepatosplenomegaly. Skin biopsy showed increased basal layer pigmentation with mildly increased collagenization, lymphocytic, and histiocytic infiltrate in the dermis. Immunohistochemistry analysis was not performed in our case. Mutational analysis of genomic DNA documented a known homozygous mutation p. Arg134Cys (c.400C>T) in exon 4 of SLC29A3 gene and heterozygous state in parents and siblings confirming the diagnosis of H syndrome [Figure 2].
Figure 1: (a and b) Bilateral symmetrical hyperpigmented, indurated plaque with hypertrichosis on extensor and posterior aspect of thighs and lower legs sparing the knee joint, gluteal region and part of popliteal fossa, (c) involvement of lumbosacral region, (d) and dorsum of feet with hallus valgus

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Figure 2: SLC29A3 gene homozygous known mutation of p.Arg134Cys (c.400 C>T) in proband and heterozygous state in father, mother and siblings

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Other associated clinical features described in literature are episcleritis, glaucoma, pancreatic exocrine deficiency, complete agenesis of inferior vena cava with varicose veins, facial telangiectasia, flexion contractures of fingers and toes, camptodactyly, multiple bone fractures, osteoporosis, brachydactyly, bone sclerosis, hyperostosis, gluteal lipodystrophy, arthritis, genital masses, micropenis, azoospermia, hypoplastic uterus, hydronephrosis, renal cortical cysts with calcification, hematological abnormalities, and hydrocephalus.[4],[5],[6]

Genotype-phenotype correlation has not been done so far due to interfamilial and intrafamilial clinical variability. She was earlier elsewhere diagnosed with mucopolysaccharidoses and investigated for several years due to overlapping systemic features. Differential diagnosis includes Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes (POEMS) syndrome,  Rosai-Dorfman Disease More Details, hemochromatosis, and various inflammatory disorders.[4] However, pathognomonic cutaneous features of H syndrome rule out other differential diagnosis. There is no specific treatment of this disorder and is mainly supportive. Genetic counseling is important in management. This case is presented to increase the awareness of this condition among both dermatologists and pediatricians as it can be easily misdiagnosed.

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.


VR acknowledges the support of the Indian Council of Medical Research for their financial support given to her through the project “Investigations of Association of Mutations in MODY and NDM by Translational Genomic Research.“

Financial support and sponsorship

Indian Council of Medical Research.

Conflicts of interest

There are no conflicts of interest.

  References Top

Mehta S, Masatkar V, Mittal A, Khare AK, Gupta LK. The H syndrome. Indian J Paediatr Dermatol 2015;16:102-4.  Back to cited text no. 1
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Yesudian P, Sarveswari KN, Karrunya KJ, Thomas K. H syndrome – A case report. Indian Dermatol Online J 2019;10:300-2.  Back to cited text no. 2
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Molho-Pessach V, Lerer I, Abeliovich D, Agha Z, Abu Libdeh A, Broshtilova V, et al. The H syndrome is caused by mutations in the nucleoside transporter hENT3. Am J Hum Genet 2008;83:529-34.  Back to cited text no. 3
Molho-Pessach V, Ramot Y, Camille F, Doviner V, Babay S, Luis SJ, et al. H syndrome: The first 79 patients. J Am Acad Dermatol 2014;70:80-8.  Back to cited text no. 4
Molho-Pessach V, Varma M, Godbole K, Kamath N, Zlotogorski A. H syndrome – Four new patients from India. Indian J Dermatol Venereol Leprol 2014;80:579.  Back to cited text no. 5
[PUBMED]  [Full text]  
Priya TP, Philip N, Molho-Pessach V, Busa T, Dalal A, Zlotogorski A. H syndrome: Novel and recurrent mutations in SLC29A3. Br J Dermatol 2010;162:1132-4.  Back to cited text no. 6


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