Carolyn A. Bay, M.D., Kurt Wegner, M.D., Jacquelyn Mang, M.S., M. Barudi, M.D., M. Ayas, M.D., and Michael Saalouke, M.D., Department of Pediatirics, Northeastern Ohio Universities College of Medicine, Tod Children's Hospital, 500 Gypey Lane, Youngstown, OH 44501, (216) 740-3106 or 740-3356



Kabuki Makeup syndrome has occasionally been associated with medical problems, including neonatal hypoglycemia, and a single reported case of idiopathic thrombocytopenia purpura (ITP). We have investigated a patient with several previously unreported medical complications, who developed an unusual form of ITP.

She is currently an 8 year old white female. Dysmorphic features included: blue sclerae, extremely long palpebral fissures, mildly everted lower eyelids, prominent ears, hypodontia, early breast development, hyperextensibility of thumbs and MCP joints, and increased size of finger fat pads. Her growth demonstrated postnatal growth deceleration, but not short stature. Investigations revealed eventration of the diaphragm, a VSD, a malrotated kidney and megaloureter. She has attention deficit disorder with hyperactivity, and mild developmental delays, with mild feeding problems.

Previously unreported or unusual features include:

1) IgA deficiency, with mild decrease in IgG. Extremely low IgA, mildly low IgG and normal IgM; with frequent infections of the skin, respiratory tract, kidneys, and otitis media. Virtually all skin wounds become infected.

2) Chronic Relapsing form of ITP, presenting at 4 years of age, documented by bone marrow examination, with occasional mild concomitant neutropenia. Exacerbations of ITP are usually associated with viral illnesses. She has normal platelet counts between episodes. The ITP initially responded to minimal doses of prednisone (1 mg/kg x 3 days), but now is requiring higher doses to achieve remission. She had an adverse reaction with intravenous immunoglobulin infusion, possibly related to the presence of IgA in the infusion.

3) Recurrent reactive airway disease

4) Persistent Hypoglycemia. Initially noted in the first day of life, requiring IV dextrose. She required frequent feedings, including through the night until 4 1/2 years of age. Currently, she can sleep through the night without becoming hypoglycemic, however illnesses associated with fasting states still require frequent feedings, and occasionally IV dextrose. Inpatient evaluation in CRC at 4 years of age was unsuccessful in identifying an etiology for the hypoglycemia.

Our findings suggest that immunologic mechanisms may play an important role in the pathophysiology of some of the clinical findings in the Kabuki makeup syndrome. IgA deficiency may be an etiology of respiratory or skin infections, or diarrhea; and could be associated with anaphylaxis in IgA sensitized patients receiving immunoglobulins. ITP may be atypical. Clinicians should be alerted to the possibility of persistent hypoglycemia.


Hypoglycemia is occasionally mentioned, but only that, mentioned. It always appears to be mentioned about a newborn (during the neonatal period). For instance:

Long-term hormone replacement therapy in two patients with Kabuki syndrome and growth hormone deficiency - Minerva Pediatr Jan-Feb;52(1-2) pp. 47-53 2000 Author: : Gabrielli O, Carloni L, Coppa GV, Bedeschi MF, Petroncini MM, Selicorni A

1st page (47) - "Cases of KS with dysfunction of the hypophysis causing diabetes insipidus and growth hormone deficiency, and isolated idiopathic precocious puberty have been also reported in literature."

Page 50 - "During the first year of life he had a number of seizures associated with hypoglycaemia and generalized hypotonia."

Note: in looking at this article's bibliography, the case of diabetes insipidus is likely from the article:

A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction - Acta Paediatrica Japonica 36 pp.412-415 1994 Author: Tawa R, et al.

Other articles which mention hypoglycemia:

Severe Congenital Anomalies Requiring Transplantation in Children with Kabuki Syndrome - American Journal of Medical Genetics 80(4) pp.362-367 1998 Author: Ewart-Toland A, et al.

1st page - "At birth case 1 presented with hypoglycemia...."

Kabuki syndrome - Report of six cases and review of the literature with emphasis on ocular features - Ophthalmic Genetics Mar;21(1) pp. 51-61 2000 Author: Kluijt I, van Dorp DB, Kwee ML, Toutain A, Keppler-Noreuil K, Warburg M, Bitoun P.

Case 1 - hypoglycemia and hypocalcemia during 1st days of life

Thirteen cases of Niikawa-Kuroki syndrome: report and review with emphasis on medical complications and preventive management - American Journal of Medical Genetics 79 pp. 112-120 1998 Author: Wilson, G. N.

Case 5 - hypoglycemia after birth

Case 9 - transient hypoglycemia during neonatal period

CNS malformation in a child with Kabuki (Niikawa-Kuroki) syndrome: report and review - American Journal of Medical Genetics 72(2) pp.205-209 1997 Author: Chu DC, et al.

Page 207 - Table 1: 12% previous cases had hypoglycemia